proteinopathies

Proteinopathies are diseases characterized by the abnormal folding, misfolding, aggregation, or deposition of specific proteins within cells or tissues. These protein aggregates can disrupt cellular function and lead to cell death. Proteinopathies are most studied in the nervous system, but they can affect other organs as well.

In neurodegenerative disease, common proteinopathies include Alzheimer's disease, where amyloid-beta plaques and tau tangles accumulate; Parkinson's disease, with alpha-synuclein aggregates known as Lewy bodies; and certain forms of frontotemporal dementia, which may involve tau or TDP-43 aggregates. Prion diseases, such as Creutzfeldt-Jakob disease, involve misfolded prion protein that can template further misfolding and, in some cases, transmit between individuals. Systemic amyloidoses, including transthyretin and immunoglobulin light-chain amyloidosis, involve extracellular deposition of misfolded proteins in organs.

Pathophysiology often involves templated misfolding and, in some cases, prion-like spread of aggregates within tissues. Impairments in proteostasis networks—molecular chaperones, the ubiquitin–proteasome system, and autophagy—permit accumulation of misfolded proteins. Toxic species are frequently soluble oligomers, which can disrupt membranes, signaling, and protein quality control before large aggregates form.

Diagnosis combines clinical assessment with biomarkers and imaging. For Alzheimer’s and related disorders, cerebrospinal fluid assays and PET imaging of amyloid and tau, along with genetic testing for familial forms, are used. Treatments are mainly supportive; disease-modifying therapies targeting specific proteins are under development, and a few have regulatory approval in select contexts. Research continues to understand mechanisms and to develop strategies that enhance clearance or prevent aggregation.

Proteinopathies remain a major area of biomedical study due to their prevalence and impact on function and quality of life.